益气活血通络汤治疗原发性高血压合并糖耐量减低临床研究

目的:观察中药益气活血通络汤治疗高血压合并糖耐量减低的临床疗效。方法:将64例高血压合并糖尿病患者,随机分为2组各32例,对照组口服硝苯地平片治疗;观察组加用中药益气活血通络汤,以治疗前后收缩压(SBP)、舒张压(DBP)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、血糖、胰岛素、胰岛素敏感性指数(ISI)、胰岛素抵抗指数(HOMA-IR)为观察指标。结果:治疗3个月后,观察组疗效优于对照组(Z=-1.998,P<0.05)。与治疗前比较,2组经治疗后SBP、DBP、TC、TG、LDL-C均下降,HDL-C上升,差异有统计学意义(P<0.05);观察组治疗后SBP、DBP、TC、TG、LDL-C、HDL-C与对照组治疗后比较,差异有统计学意义(P<0.05)。与治疗前比较,2组经治疗后空腹和餐后2 h血糖、胰岛素、HOMA-IR均下降,ISI上升,差异有统计学意义(P<0.05);且经治疗后,观察组上述所有指标改善情况均优于对照组,差异有统计学意义(P<0.05)。2组患者在3个月的治疗期间中均未出现严重不良反应。结论:中药益气活血通络汤治疗高血压合并糖耐量降低疗效较好且安全性高,能显著降低血压,改善血脂。     

基因间长链非编码RNA152靶向微小RNA?103a?3p对非小细胞肺癌细胞增殖和侵袭迁移的影响

目的探讨基因间长链非编码RNA 152(LINC00152)靶向调控微小RNA-103a-3p(miR-103a-3p)表达及对非小细胞肺癌(NSCLC)细胞增殖和侵袭迁移的影响。方法采用实时定量PCR(QPCR)检测正常肺上皮细胞BEAS-2B及NSCLC细胞(ANIP-973、NCI-H157、A549和NCI-H1975)的LINC00152水平。选取LINC00152水平最高的细胞分别转染LINC00152特异性小干扰RNA(si-LINC00152组)或无关序列(si-NC组),另设未转染细胞为对照组。QPCR检测LINC00152水平,活细胞计数CCK-8法、Transwell小室和划痕实验测定细胞增殖、侵袭和迁移能力,Western blotting检测基质金属蛋白酶(MMP)-2、MMP-9和第10号染色体缺失的磷酸酶及张力蛋白同源基因(PTEN)的水平;荧光素酶报告实验验证LINC00152靶向结合miR-103a-3p的能力。结果NSCLC细胞的LINC00152水平均高于BEAS-2B细胞(P<0.05),尤其是NCI-H1975细胞的最高。si-LINC00152组的LINC00152水平为0.352±0.087,低于对照组的1.058±0.219和si-NC组的1.126±0.139(P<0.05)。与si-NC组和对照组相比,si-LINC00152组NCI-H1975细胞转染48、72 h的增殖活力下降(P<0.05);si-LINC00152组的划痕愈合率和穿膜细胞数分别为(27.386±2.428)%和(78.840±5.031)个,低于si-NC组的(77.675±4.803)%和(179.208±13.264)个及对照组的(76.371±5.385)%和(174.003±15.678)个(P<0.05);与si-NC组和对照组相比,si-LINC00152组的MMP-2和MMP-9水平均降低,而PTEN水平升高(P<0.05)。对照组和si-NC组上述指标的差异无统计学意义(P>0.05)。双荧光素酶报告分析证实,miR-103a-3p模拟物降低了野生型LINC00152的荧光素酶活性(P<0.05),但对突变型无影响(P>0.05)。结论LINC00152在NSCLC细胞中高表达并发挥促癌作用,与NSCLC的迁移侵袭密切相关,LINC00152与miR-103a-3p间的相互作用在NSCLC靶向治疗中有一定潜能。     

Recent advances in preclinical in vitro approaches towards quantitative prediction of hepatic clearance and drug-drug interactions involving organic anion transporting polypeptide (OATP) 1B transporters

Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CL_h) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CL_h involving OATP1B-mediated hepatic uptake. CL_h can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CL_h and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction.     

中低度近视SMILE术后超早期视觉质量变化的研究

目的观察飞秒激光小切口角膜基质透镜取出术(SMILE)术后超早期患者视觉质量变化,探讨其变化发生的可能原因。方法选取中低度近视患者23例46眼行SMILE术,术前及术后24 h超早期行主观视觉质量问卷,测量最佳矫正视力的全程视力(远视力5 m,中视力60 cm,近视力33 cm)、对比敏感度(CS)、眩光敏感度(GS)及集合近点(NPC)和调节幅度(AA)。结果视觉质量主观问卷显示术后超早期主观视觉质量较术前下降(P=0.001)。术后裸眼视力(UCVA)明显提高(P=0.0001)。术前与术后最佳矫正视力(BCVA)中远视力没有变化(P=0.096),而中视力和近视力均较术前下降(P=0.039,0.003)。术后CS、GS降低(PCS=0.0001,PGS=0.04),NPC、AA较术前无明显变化(P=0.68,0.13)。结论SMILE术后超早期患者可获得预期理想远视力,但中、近视力尚未恢复。超早期中出现的异常视觉质量改变可能与对比敏感度和眩光敏感度的改变有关。     

Epigenetics explained: a topic “primer” for the epilepsy community by the ILAE Genetics/Epigenetics Task Force

Epigenetics refers broadly to processes that influence medium to long‐term gene expression by changing the readability and accessibility of the genetic code. The Neurobiology Commission of the International League Against Epilepsy (ILAE) recently convened a Task Force to explore and disseminate advances in epigenetics to better understand their role and intersection with genetics and the neurobiology of epilepsies and their co‐morbidities, and to accelerate translation of these findings into the development of better therapies. Here, we provide a topic primer on epigenetics, explaining the key processes and findings to date in experimental and human epilepsy. We review the growing list of genes with epigenetic functions that have been linked with epilepsy in humans. We consider potential practical applications, including using epigenetic signals as biomarkers for tissue‐ and biofluid‐based diagnostics and the prospects for developing epigenetic‐based treatments for epilepsy. We include a glossary of terms, FAQs and other supports to facilitate a broad understanding of the topic for the non‐expert. Last, we review the limitations, research gaps and the next challenges. In summary, epigenetic processes represent important mechanisms controlling the activity of genes, providing opportunities for insight into disease mechanisms, biomarkers and novel therapies for epilepsy.     

桃红四物汤化学成分、药理作用、临床应用的研究进展及质量标志物的预测分析

桃红四物汤,活血祛瘀之经典名方。该文对近年来桃红四物汤的化学成分、药理作用以及临床应用研究进展进行总结与分析。目前,桃红四物汤不同提取部位化学成分的研究较为系统,其药理作用研究主要集中在活血化瘀、调经镇痛、促进骨折愈合等方面,临床可应用于多系统、多脏腑疾病的治疗,例如妇科疾病、内科疾病、骨伤科疾病、皮肤科疾病等。在此基础上,依照质量标志物(Q-marker)有效、特有、传递与溯源、可测和处方配伍的"五原则"对桃红四物汤Q-marker进行预测分析,提示阿魏酸、芍药苷、苦杏仁苷、芍药内酯苷、梓醇、没食子酸、羟基红花黄色素A可作为该复方的Q-marker,后续可选择这些Q-marker为指标,根据药材、饮片、中间体、对应实物的量值传递进行桃红四物汤全程质量控制并创建其质量可溯源体系。